The genetics, neuropathology, and clinical presentation is complex, diverse, and often overlapping among the various types of dementias. However, differential diagnosis is critical. Although disease-modifying treatments for virtually all forms of non-reversible dementias have yet to be discovered, an accurate differential diagnosis is key in order to design clinical trials aimed at discovering novel treatments for different causes of dementia. Additionally, the use of certain neuroleptics may have some benefit (albeit limited) in select dementias (e.g., cholinesterase inhibitors for Alzheimer's disease) but may be ineffective and possibly contraindicated in other dementias (e.g., cholinesterase inhibitors in frontotemporal lobar degeneration disorders). The understanding of the complex diagnosis and neurobiological substrates underlying each form of dementia is critical to the effective management of patients as well as the development of potential disease-modifying treatments and lifestyle strategies aimed at reducing one's risk of developing dementia.